Advertisement

Journal of Endocrinological Investigation

, Volume 35, Issue 9, pp 824–827 | Cite as

Asymmetric dimethylarginine and carotid atherosclerosis in Type 2 diabetes mellitus

  • W. Xia
  • Y. Shao
  • Y. Wang
  • X. Wang
  • Y. Chi
Original Article

Abstract

Background: Circulating asymmetric dimethylarginine (ADMA) concentration is elevated in patients with Type 2 diabetes mellitus (T2DM). Aim: To assess the relationship between plasma ADMA concentration and carotid atherosclerosis in patients with T2DM. Subjects and methods: A total of 72 newly diagnosed and untreated T2DM individuals and 72 healthy controls were studied. Carotid atherosclerosis was determined by ultrasonographically evaluated intima-media thickness (IMT) and plaque score. Plasma concentration of ADMA was measured by high-performance liquid chromatography. Results: Plasma ADMA, mean IMT, and plaque score were higher in diabetic patients compared with controls. Univariate and multivariate analyses demonstrated an independent association between ADMA and mean IMT in diabetic patients. On a multiple logistic regression analysis, ADMA was the sole predictor of carotid plaque formation (plaque score ≥1.1) (odds ratio 2.43, 95% confidence interval 1.19 to 4.94, p<0.05). Conclusion: Our results suggest that increased levels of ADMA might be involved in the development of carotid atherosclerosis in T2DM.

Key-words

Asymmetric dimethylarginine atherosclerosis intima-media thickness Type 2 diabetes mellitus 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Vallance P, Leone A, Calver A, Collier J, Moncada S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992, 339: 572–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Böger RH. The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor. Cardiovasc Res 2003, 59: 824–33.PubMedCrossRefGoogle Scholar
  3. 3.
    Krzyzanowska K, Mittermayer F, Wolzt M, Schernthaner G. ADMA, cardiovascular disease and diabetes. Diabetes Res Clin Pract 2008, 82: S122–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Mudríková T, Szabová E, Tkác I. Carotid intima-media thickness in relation to macrovascular disease in patients with type 2 diabetes mellitus. Wien Klin Wochenschr 2000, 112: 887–91.PubMedGoogle Scholar
  5. 5.
    Nanayakkara PW, Teerlink T, Stehouwer CD, et al. Plasma asymmetric dimethylarginine (ADMA) concentration is independently associated with carotid intima-media thickness and plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) concentration in patients with mild-to-moderate renal failure. Kidney Int 2005, 68: 2230–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Furuki K, Adachi H, Enomoto M, et al. Plasma level of asymmetric dimethylarginine (ADMA) as a predictor of carotid intima-media thickness progression: six-year prospective study using carotid ultrasonography. Hypertens Res 2008, 31: 1185–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Abbasi F, Asagmi T, Cooke JP, et al. Plasma concentrations of asymmetric dimethylarginine are increased in patients with type 2 diabetes mellitus. Am J Cardiol 2001, 88: 1201–3.PubMedCrossRefGoogle Scholar
  8. 8.
    Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998, 15: 539–53.PubMedCrossRefGoogle Scholar
  9. 9.
    Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972, 18: 499–502.PubMedGoogle Scholar
  10. 10.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and B-cell function from plasma glucose and insulin concentrations in man. Diabetologia 1985, 28: 412–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Teerlink T, Nijveldt RJ, de Jong S, van Leeuwen PA. Determination of arginine, asymmetric dimethylarginine, and symmetric dimethylarginine in human plasma and other biological samples by high-performance liquid chromatography. Anal Biochem 2002, 303: 131–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Kondo K, Kitagawa K, Nagai Y, et al. Associations of soluble intercellular adhesion molecule-1 with carotid atherosclerosis progression. Atherosclerosis 2005, 179: 155–60.PubMedCrossRefGoogle Scholar
  13. 13.
    Altinova AE, Arslan M, Sepici-Dincel A, Akturk M, Altan N, Toruner FB. Uncomplicated type 1 diabetes is associated with increased asymmetric dimethylarginine concentrations. J Clin Endocrinol Metab 2007, 92: 1881–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Mittermayer F, Mayer BX, Meyer A, et al. Circulating concentrations of asymmetrical dimethyl-L-arginine are increased in women with previous gestational diabetes. Diabetologia 2002, 45: 1372–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Stühlinger MC, Abbasi F, Chu JW, et al. Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. JAMA 2002, 287: 1420–6.PubMedCrossRefGoogle Scholar
  16. 16.
    McLaughlin T, Stühlinger M, Lamendola C, et al. Plasma asymmetric dimethylarginine concentrations are elevated in obese insulin-resistant women and fall with weight loss. J Clin Endocrinol Metab 2006, 91: 1896–900.PubMedCrossRefGoogle Scholar
  17. 17.
    Lajer M, Tarnow L, Jorsal A, Teerlink T, Parving HH, Rossing P. Plasma concentration of asymmetric dimethylarginine (ADMA) predicts cardiovascular morbidity and mortality in type 1 diabetic patients with diabetic nephropathy. Diabetes Care 2008, 31: 747–52.PubMedCrossRefGoogle Scholar
  18. 18.
    Malecki MT, Undas A, Cyganek K, et al. Plasma asymmetric dimethylarginine (ADMA) is associated with retinopathy in type 2 diabetes. Diabetes Care 2007, 30: 2899–901.PubMedCrossRefGoogle Scholar
  19. 19.
    Kanazawa I, Yano S, Notsu Y, Yamaguchi T, Nabika T, Sugimoto T. Asymmetric dimethylarginine as a risk factor for cardiovascular disease in Japanese patients with type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2011, 74: 467–72.CrossRefGoogle Scholar
  20. 20.
    Fard A, Tuck CH, Donis JA, et al. Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes. Arterioscler Thromb Vasc Biol 2000, 20: 2039–44.PubMedCrossRefGoogle Scholar
  21. 21.
    Xiong Y, Fu YF, Fu SH, Zhou HH. Elevated levels of the serum endogenous inhibitor of nitric oxide synthase and metabolic control in rats with streptozotocin-induced diabetes. J Cardiovasc Pharmacol 2003, 42: 191–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Yasuda S, Miyazaki S, Kanda M, et al. Intensive treatment of risk factors in patients with type-2 diabetes mellitus is associated with improvement of endothelial function coupled with a reduction in the levels of plasma asymmetric dimethylarginine and endogenous inhibitor of nitric oxide synthase. Eur Heart J 2006, 27: 1159–65.PubMedCrossRefGoogle Scholar
  23. 23.
    Napoli C, de Nigris F, Williams-Ignarro S, Pignalosa O, Sica V, Ignarro LJ. Nitric oxide and atherosclerosis: an update. Nitric Oxide 2006, 15: 265–79.PubMedCrossRefGoogle Scholar
  24. 24.
    Barbato JE, Tzeng E. Nitric oxide and arterial disease. J Vasc Surg 2004, 40: 187–93.PubMedCrossRefGoogle Scholar
  25. 25.
    Böger RH, Bode-Böger SM, Szuba A, et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 1998, 98: 1842–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Böger RH, Bode-Böger SM, Thiele W, Junker W, Alexander K, Frölich JC. Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease. Circulation 1997, 95: 2068–74.PubMedCrossRefGoogle Scholar
  27. 27.
    Dayoub H, Achan V, Adimoolam S, et al. Dimethylarginine dimethylaminohydrolase regulates nitric oxide synthesis: genetic and physiological evidence. Circulation 2003, 108: 3042–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Chan JR, Böger RH, Bode-Böger SM, et al. Asymmetric dimethylarginine increases mononuclear cell adhesiveness in hypercholesterolemic humans. Arterioscler Thromb Vasc Biol 2000, 20: 1040–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Böger RH, Bode-Böger SM, Tsao PS, Lin PS, Chan JR, Cooke JP. An endogenous inhibitor of nitric oxide synthase regulates endothelial adhesiveness for monocytes. J Am Coll Cardiol 2000, 36: 2287–95.PubMedCrossRefGoogle Scholar
  30. 30.
    Smirnova IV, Kajstura M, Sawamura T, Goligorsky MS. Asymmetric dimethylarginine upregulates LOX-1 in activated macrophages: role in foam cell formation. Am J Physiol Heart Circ Physiol 2004, 287: H782–90.PubMedCrossRefGoogle Scholar
  31. 31.
    Nishikawa T, Edelstein D, Du XL, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000, 404: 787–90.PubMedCrossRefGoogle Scholar
  32. 32.
    Suda O, Tsutsui M, Morishita T, et al. Asymmetric dimethylarginine produces vascular lesions in endothelial nitric oxide synthasedeficient mice: involvement of renin-angiotensin system and oxidative stress. Arterioscler Thromb Vasc Biol 2004, 24: 1682–8.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2012

Authors and Affiliations

  1. 1.Department of Cardiology, Qingdao Municipal Hospitalthe Affiliated Hospital of Ocean University of ChinaShandongChina

Personalised recommendations